A Phase II, Pharmacokinetic and Biologic Correlative Study of Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Advanced Renal Cell Carcinoma (RCC)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed diagnosis of advanced renal cell carcinoma
that is either metastatic or inoperable

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques OR ≥ 10 mm by spiral CT scan

- Disease is recurrent or refractory to interleukin-2 (IL-2) or interferon-based
therapy OR new diagnosis in previously untreated patients who are not appropriate
candidates to receive IL-2 based treatment

- Patients who have failed up to 4 lines of prior immunotherapy or biological
therapy allowed

- No known brain metastases or leptomeningeal disease

- Stable brain metastases or curatively resected brain metastases without
neurologic dysfunction for ≥ 6 months allowed

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2 OR Karnofsky 70-100%

- Life expectancy ≥ 12 weeks

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9.0 g/dL

- Serum creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance > 50
mL/min

- Total bilirubin within normal limits

- AST/ALT ≤ 2.5 times ULN (≤ 5 times ULN if liver metastasis is present)

- No history of active malignancy (other than renal cell carcinoma) within the past 3
years other than nonmelanomatous skin cancer, in situ breast cancer, or in situ
cervical cancer

- No history of allergic reactions to compounds of similar chemical or biological
composition to vorinostat (SAHA)

- No uncontrolled concurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
arrhythmia

- No psychiatric illness or social situation that would preclude study compliance

- No clinically significant hypercalcemia

- No significant traumatic injury within the past 21 days

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No gastrointestinal disease resulting in an inability to take oral medication

- No requirement for IV alimentation

- No active peptic ulcer disease

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from prior therapy

- Prior nephrectomy or resection of metastatic lesions allowed provided full surgical
recovery has occurred

- No chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin)

- No radiotherapy within the past 4 weeks

- No valproic acid for at least 2 weeks prior to study enrollment

- No major surgery within the past 21 days

- No prior surgical procedures affecting absorption

- No concurrent antiretroviral therapy for HIV-positive patients

- No other concurrent investigational agents

- No other concurrent anticancer therapy